Genetic profiling of fatty acid desaturase polymorphisms identifies patients who may benefit from high-dose omega-3 fatty acids in cardiac remodeling after acute myocardial infarction-Post-hoc analysis from the OMEGA-REMODEL randomized controlled trial

• Published in: PloS one 2019-09, Vol.14 (9), p.e0222061
• Main Authors: Kwong, Raymond Y, Heydari, Bobak, Ge, Yin, Abdullah, Shuaib, Fujikura, Kana, Kaneko, Kyoichi, Harris, William S, Jerosch-Herold, Michael, Antman, Elliott M, Seidman, Jonathan G, Pfeffer, Marc A
• Format: Article
• Language: English
• Subjects: Adenine; Aged; Analysis; Arachidonic acid; Arachidonic Acid - blood; Attenuation; Biology and Life Sciences; Brain natriuretic peptide; Cardiovascular disease; Care and treatment; Clinical trials; Criminal investigation; Desaturase; Double-Blind Method; Drug dosages; Enzymes; Fatty Acid Desaturases - genetics; Fatty acids; Fatty Acids, Omega-3 - administration & dosage; Fatty Acids, Omega-3 - pharmacology; Female; Fibrosis; Galectin-3; Gene polymorphism; Genes; Genetic aspects; Genetic polymorphisms; Genomes; Genotypes; Guanine; Heart; Heart attack; Heart attacks; Hospitals; Humans; Inflammation; Linoleic acid; Linoleic Acid - blood; Lipids; Male; Medicine; Medicine and Health Sciences; Middle Aged; Myocardial infarction; Myocardial Infarction - blood; Myocardial Infarction - drug therapy; Myocardial Infarction - genetics; Natriuretic peptides; Omega 3 fatty acids; Patients; Peptides; Pharmacogenomic Variants; Polymorphism; Polymorphism, Single Nucleotide; Polyunsaturated fatty acids; Prospective Studies; Pulmonary arteries; Purines; Retirement benefits; Tertiary Care Centers; Treatment Outcome; Ventricular Remodeling - drug effects; Womens health
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0222061

The double-blind OMEGA-REMODEL placebo-controlled randomized trial of high-dose omega-3 fatty acids (O-3FA) post-acute myocardial infarction (AMI) reported improved cardiac remodeling and attenuation of non-infarct myocardial fibrosis. Fatty acid desaturase 2 (FADS2) gene cluster encodes key enzymes in the conversion of essential omega-3 and omega-6 fatty acids into active arachidonic (ArA) and eicosapentaenoic acids (EPA), which influence cardiovascular outcomes. We tested the hypothesis that the genotypic status of FADS2 (rs1535) modifies therapeutic response of O-3FA in post-AMI cardiac remodeling in 312 patients. Consistent with known genetic polymorphism of FADS2, patients in our cohort with the guanine-guanine (GG) genotype had the lowest FADS2 activity assessed by arachidonic acid/linoleic acid (ArA/LA) ratio, compared with patients with the adenine-adenine (AA) and adenine-guanine (AG) genotypes (GG:1.62±0.35 vs. AA: 2.01±0.36, p